Methanol is a fermentative material that is available in a large amount at a low cost and is very useful as a carbon source. There have been developed a method of producing an L-amino acid by a methanol-assimilating bacterium using methanol as a major carbon source (Patent Document 1) and a method of producing a polysaccharide using a methanol-assimilating bacterium (Patent Document 2).
Also, there have been known an example of production of lacZ in bacterial cells using a promoter of an alcohol oxidase (AOX) gene by induction with methanol in Pichia yeast (Non-Patent Document 1) and an example of secretion of aprotinin (bovine-derived pancreatic trypsin inhibitor) as an active form in a culture supernatant (Non-Patent Document 2).
Further, there has been known an example of accumulation of a fluorescent protein (GFP) in a cell of a non-obligate methanol-assimilating bacterium, Methylobacterium extorquens, which is one of methanol-assimilating bacteria (Patent Document 3 and Non-Patent Document 3). However, there has not been known an example of secretion of a protein out of cells of an obligate methanol-assimilating bacterium.
Patent Document 1: EP 1,188,822
Patent Document 2: JP 11-56384 A
Patent Document 3: WO 2003/046226 A1
Non-patent Document 1: Nucleic Acids Res. 1987 May 11; 15(9):3859-76.
Non-patent Document 2: J Ind Microbiol. 1991 April; 7(3):197-201.
Non-patent Document 3: FEMS Microbiol Lett. 2000 Dec. 15; 193(2):195-200